Injectable nanofiber microspheres modified with metal phenolic networks for effective osteoarthritis treatment

Yujie Chen; Wei Xu; Muhammad Shafiq; Daiying Song; Tao Wang; Zhengchao Yuan; Xianrui Xie; Xiao Yu; Yihong Shen; Binbin Sun; Yu Liu; Xiumei Mo

doi:10.1016/j.actbio.2022.11.040

Injectable nanofiber microspheres modified with metal phenolic networks for effective osteoarthritis treatment

Acta Biomater. 2023 Feb:157:593-608. doi: 10.1016/j.actbio.2022.11.040. Epub 2022 Nov 24.

Authors

Yujie Chen¹, Wei Xu², Muhammad Shafiq³, Daiying Song⁴, Tao Wang⁵, Zhengchao Yuan¹, Xianrui Xie⁶, Xiao Yu¹, Yihong Shen¹, Binbin Sun¹, Yu Liu⁷, Xiumei Mo⁸

Affiliations

¹ Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Songjiang, Shanghai 201600, China.
² Research Institute of Plastic Surgery, Wei Fang Medical College, Weifang 261000, China; Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200001, China; Department of Plastic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China.
³ Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Songjiang, Shanghai 201600, China; Department of Chemical Engineering, Faculty of Engineering, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. Electronic address: [email protected].
⁴ Research Institute of Plastic Surgery, Wei Fang Medical College, Weifang 261000, China; Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200001, China.
⁵ Department of Plastic and Cosmetic Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200001, China.
⁶ School of Pharmacy, Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai 264003, China.
⁷ Research Institute of Plastic Surgery, Wei Fang Medical College, Weifang 261000, China; Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Huangpu, Shanghai 200001, China. Electronic address: [email protected].
⁸ Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Songjiang, Shanghai 201600, China. Electronic address: [email protected].

PMID: 36435438
DOI: 10.1016/j.actbio.2022.11.040

Abstract

Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases, which accounts for a large proportion of physical disabilities worldwide. Herein, we fabricated injectable gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospraying technology, which were further modified with tannic acid (TA) named as TMS or metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr²⁺) and named as TSMS to enhance their bioactivity for OA therapy. The TA-modified microspheres exhibited stable porous structure and anti-oxidative activity. Notably, TSMS showed a sustained release of TA as compared to TMS, which exhibited a burst release of TA. While all types of microspheres exhibited good cytocompatibility, TSMS displayed good anti-inflammatory properties with higher cell viability and cartilage-related extracellular matrix (ECM) secretion. The TSMS microspheres also showed less apoptosis of chondrocytes in the hydrogen peroxide (H₂O₂)-induced inflammatory environment. The TSMS also inhibited the degradation of cartilage along with the considerable repair outcome in the papain-induced OA rabbit model in vivo as well as suppressed the expression level of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β). Taken together, TSMS may provide a highly desirable therapeutic option for intra-articular treatment of OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is a chronic disease, which is caused by the inflammation of joint. Current treatments for OA achieve pain relief but hardly prevent or slow down the disease progression. Microspheres are at the forefront of drug delivery and tissue engineering applications, which can also be minimal-invasively injected into the joint. Polyphenols and therapeutic ions have been shown to be beneficial for the treatment of diseases related to the joints, including OA. Herein, we prepared gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospinning incorporated electrospraying technology and functionalized them with the metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr²⁺), and assessed their potential for OA therapy both in vitro and in vivo.

Keywords: Electrospinning; Electrospray; Inflammatory response; Metal phenolic networks; Microsphere; Nanofiber; Osteoarthritis; Strontium; Tannic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chondrocytes / metabolism
Gelatin / pharmacology
Hydrogen Peroxide / pharmacology
Microspheres
Nanofibers*
Osteoarthritis* / pathology
Rabbits
Strontium / pharmacology

Substances

Gelatin
Hydrogen Peroxide
Strontium